临床新进展

平足蛋白参与炎症反应的研究进展

  • 刘诗谣 ,
  • 赵益明
展开
  • 苏州大学附属第一医院止血与血栓实验室、江苏省血液研究所 (江苏 苏州 215000 )
赵益明,医学博士,研究员,博士研究生导师,就职于苏州大学附属第一医院、江苏省血液研究所、国家卫健委血栓与止血部级重点实验室、国家血液病临床医学研究中心,美国俄克拉荷马医学研究中心访问学者,国家自然科学基金一审专家。主要研究领域涉及内科血液学的血栓与止血方向,多年来进行血栓性和出血性疾病的基础和临床研究,体外诊断试剂研制和体内抗体药物研发的转化医学研究,以及血小板与肿瘤转移及肿瘤相关的VTE的基础和应用研究。作为课题负责人主持承担科技部“重大新药创制”科技重大专项1项,国家自然科学基金面上项目3项和江苏省自然科学基金的科研项目2项等,主要研究成果在《Gastroenterology》、《eLife》、《J Hematol Oncol》、《J Thromb and Haemost》、《Biochem Pharmacol》、《Cancer Science》、《Thrombosis Research》、《Eur J Haematol》、《BMC Cancer》等国内外杂志上发表, 已获得授权的国家发明专利4项,获得国家科技进步奖二等奖一项,江苏省科学技术奖一等奖1项,教育部科技进步奖一等奖1项等科技奖,参与研制获得国家级体外诊断试剂盒药证2张。

收稿日期: 2023-02-03

  网络出版日期: 2023-09-26

基金资助

国家自然科学基金项目(81873431)

Research progress on the involvement of podoplanin in inflammatory response

  • Shiyao LIU ,
  • Yiming. ZHAO
Expand
  • Jiangsu Institute of Hematology,Hemostasis and Thrombosis Laboratory,First Affiliated Hospital of Soochow University,Suzhou 215000,China

Received date: 2023-02-03

  Online published: 2023-09-26

摘要

平足蛋白(podoplanin,PDPN)是一种较为保守的唾液酸跨膜黏蛋白,常表达于个体发育中的成纤维细胞、肺泡细胞和肾小球足细胞等不同类型的细胞组织当中,参与个体的胚胎发育、免疫反应、癌症恶性进展等过程。急性炎症是机体受到刺激时产生的一系列红、肿、热、痛的防御反应,对于机体有一定的保护作用,但当急性炎症逐步发展为慢性炎症时会对机体产生一定的有害影响而导致疾病的产生。近年来研究表明当机体产生炎症时,PDPN在各细胞组织中的表达上调,如成纤维细胞、T细胞以及巨噬细胞等,也多表达于炎症性疾病,如多发性硬化症、类风湿性关节炎和系统性硬化症等,而且PDPN主要通过与其相邻的细胞或蛋白相互作用,来调节细胞的增殖、收缩、迁移、定植等行为参与炎症性疾病的发生发展。而静脉血栓的形成与炎症密切相关,PDPN在炎症驱动血栓的形成过程中起到了一定的作用。本文主要将对PDPN的结构、功能和在炎症中的功能及作用机制的研究作一综述。

关键词: 平足蛋白; 炎症; 机制; 功能

本文引用格式

刘诗谣 , 赵益明 . 平足蛋白参与炎症反应的研究进展[J]. 实用医学杂志, 2023 , 39(16) : 2017 -2021 . DOI: 10.3969/j.issn.1006-5725.2023.16.002

Abstract

Podoplanin (PDPN) is a relatively conserved sialic acid transmembrane mucin, which is often expressed in different types of cell tissues such as fibroblasts, alveolar cells and glomerular podocytes in ontogenetic development, and participates in the embryonic development, immune response, and malignant progression of cancer. Acute inflammation is a series of red,swollen,hot,painful defense reactions when the body is stimulated,which has a certain protective effect on the body,but when acute inflammation gradually develops into chronic inflammation, it will have a certain harmful effect on the body and lead to disease. In recent years, studies have shown that when the body produces inflammation,the expression of PDPN in various cell tissues is upregulated,such as fibroblasts, T cells and macrophages, etc., and is also expressed in inflammatory diseases, such as multiple sclerosis, rheumatoid arthritis and systemic sclerosis,and PDPN mainly interacts with adjacent cells or proteins to regulate cell proliferation,contraction,migration,colonization and other behaviors to participate in the occurrence and development of inflammatory diseases. This article will mainly review the structure, function, function and mechanism of PDPN in inflammation.

参考文献

1 SINGH N, BABY D, RAJGURU J P,et al. Inflammation and cancer[J]. Ann Afr Med, 2019, 18(3): 121-126.
2 PAYNE H, PONOMARYOV T, WATSON S P,et al. Mice with a deficiency in CLEC-2 are protected against deep vein thrombosis[J]. Blood, 2017, 129(14): 2013-2020.
3 QUINTANILLA M, MONTERO-MONTERO L, RENART J,et al. Podoplanin in Inflammation and Cancer[J]. Int J Mol Sci, 2019, 20(3): 707.
4 NAVARRO A, PEREZ R E, REZAIEKHALIGH M H,et al. Polarized migration of lymphatic endothelial cells is critically dependent on podoplanin regulation of Cdc42[J]. Am J Physiol Lung Cell Mol Physiol, 2011, 300(1): L32-L42.
5 KARIN M, CLEVERS H. Reparative inflammation takes charge of tissue regeneration[J]. Nature, 2016, 529(7586): 307-315.
6 BALDWIN M J, MIMPEN J Y, CRIBBS A P,et al. Electrospun Scaffold Micro-Architecture Induces an Activated Transcriptional Phenotype within Tendon Fibroblasts[J]. Front Bioeng Biotechnol, 2022, 9: 795748.
7 ZHANG Z, ZHANG N, YU J,et al. The Role of Podoplanin in the Immune System and Inflammation[J]. J Inflamm Res, 2022, 15: 3561-3572.
8 YASUDA K, TAKEUCHI Y, HIROTA K. The pathogenicity of Th17 cells in autoimmune diseases[J]. Semin Immunopathol, 2019, 41(3): 283-297.
9 CHEOK Y Y, TAN G M Y, FERNANDEZ K C,et al. Podoplanin Drives Motility of Active Macrophage via Regulating Filamin C During Helicobacter pylori Infection[J]. Front Immunol, 2021, 12: 702156.
10 FEI M, WANG H, ZHOU M,et al. Podoplanin influences the inflammatory phenotypes and mobility of microglia in traumatic brain injury[J/OL]. Biochem Biophys Res Commun, 2020, 523(2): 361-367.
11 XIE Z, SHAO B, HOOVER C,et al. Monocyte upregulation of podoplanin during early sepsis induces complement inhibitor release to protect liver function[J]. JCI Insight, 2020, 5(13): e134749.
12 RAYES J, LAX S, WICHAIYO S,et al. The podoplanin-CLEC-2 axis inhibits inflammation in sepsis[J]. Nat Commun, 2017, 8(1): 2239.
13 LAX S, RAYES J, WICHAIYO S,et al. Platelet CLEC-2 protects against lung injury via effects of its ligand podoplanin on inflammatory alveolar macrophages in the mouse[J]. Am J Physiol Lung Cell Mol Physiol, 2017, 313(6): L1016-L1029.
14 SUZUKI-INOUE K. Platelets and cancer-associated thrombosis: focusing on the platelet activation receptor CLEC-2 and podoplanin[J]. Blood, 2019, 134(22): 1912-1918.
15 LENTI M V, ROSSI C M, MELAZZINI F,et al. Seronegative autoimmune diseases: A challenging diagnosis[J]. Autoimmun Rev, 2022, 21(9): 103143.
16 孟凡, 陈峻, 刘雨霞,等, Dock 2通过调节T细胞活性和抗原特异性IgG抗体的产生来控制肠道柠檬酸杆菌感染 [J]. 实用医学杂志, 2021, 37(8): 1000-1007.
17 ORANGE D E, YAO V, SAWICKA K,et al. RNA Identification of PRIME Cells Predicting Rheumatoid Arthritis Flares[J/OL]. N Engl J Med, 2020, 383(3): 218-228.
18 ASAI J. The Role of Podoplanin in Skin Diseases[J]. Int J Mol Sci, 2022, 23(3): 1310.
19 CIMINI M, KISHORE R. Role of Podoplanin-Positive Cells in Cardiac Fibrosis and Angiogenesis After Ischemia[J]. Front Physiol, 2021, 12: 667278.
20 CARPINTERO-FERNANDEZ P, VARELA-EIRIN M, LACETERA A,et al. New Therapeutic Strategies for Osteoarthritis by Targeting Sialic Acid Receptors[J]. Biomolecules, 2020, 10(4): 637.
21 HUANG Y, LU M, WANG Y,et al. Podoplanin: A potential therapeutic target for thrombotic diseases[J]. Front Neurol, 2023, 14: 1118843.
22 MENG D, LUO M, LIU B. The Role of CLEC-2 and Its Ligands in Thromboinflammation[J]. Front Immunol, 2021, 12: 688643.
23 MENG D, MA X, LI H,et al. A Role of the Podoplanin-CLEC-2 Axis in Promoting Inflammatory Response After Ischemic Stroke in Mice[J]. Neurotox Res,2021, 39(2): 477-488.
24 NAKATA Y, KONO H, AKAZAWA Y,et al. Role of podoplanin and Kupffer cells in liver injury after ischemia-reperfusion in mice[J]. Surg Today, 2022, 52(2): 344-353.
25 QIAN S, QIAN L, YANG Y,et al. Podoplanin neutralization reduces thrombo-inflammation in experimental ischemic stroke by inhibiting interferon/caspase-1/GSDMD in microglia[J]. Ann Transl Med, 2022, 10(18): 979-979.
26 QIAN S, QIAN L, YANG Y,et al. Transcriptome sequencing analysis revealed the molecular mechanism of podoplanin neutralization inhibiting ischemia/reperfusion-induced microglial activation[J]. Ann Transl Med, 2022, 10(11): 638.
文章导航

/